Flush perfusion of the pulmonary artery with organ protection solution is a standard procedure before lung explantation. However, rapid flush perfusion may cause pulmonary oedema which is deleterious in the lung transplantation setting. In this study we tested the hypotheses that high pulmonary perfusion pressure contributes to the development of pulmonary oedema and positive end-expiratory pressure (PEEP) counteracts oedema formation. We expected oedema formation to increase weight and decrease compliance of the lungs on the basis of a decrease in alveolar volume as fluid replaces alveolar air spaces. The pulmonary artery of 28 isolated porcine lungs was perfused with a low-potassium dextrane solution at low (mean 27 mmHg) or high (mean 40 mmHg) pulmonary artery pressure (PAP) during mechanical ventilation at low (4 cmH(2)O) or high (8 cmH(2)O) PEEP, respectively. Following perfusion and storage, relative increases in lung weight were smaller (p < 0.05) during perfusion at low PAP (62 +/- 32% and 42 +/- 26%, respectively) compared to perfusion at high PAP (133 +/- 54% and 87 +/- 30%, respectively). Compared to all other PAP-PEEP combinations, increases in lung weight were smallest (44 +/- 9% and 27 +/- 12%, respectively), nonlinear intratidal lung compliance was largest (46% and 17% respectively, both p < 0.05) and lung histology showed least infiltration of mononuclear cells in the alveolar septa, and least alveolar destruction during the combination of low perfusion pressure and high PEEP. The findings suggest that oedema formation during pulmonary artery flush perfusion in isolated and ventilated lungs can be reduced by choosing low perfusion pressure and high PEEP. PAP-PEEP titration to minimize pulmonary oedema should be based on lung mechanics and PAP monitoring.